Metabolic tumor burden quantified on [¹⁸F]FDG PET/CT improves TNM staging of lung cancer patients

Purpose: The purpose of our study was to test a new staging algorithm, combining clinical TNM staging (cTNM) with whole-body metabolic active tumor volume (MATV-WB), with the goal of improving prognostic ability and stratification power.

Methods: Initial staging [¹⁸F]FDG PET/CT of 278 non-small cell lung cancer (NSCLC) patients, performed between January/2011 and April/2016, 74(26.6%) women, 204(73.4%) men; aged 34-88 years (mean ± SD:66 ± 10), was retrospectively evaluated, and MATV-WB was quantified. Each patient's follow-up time was recorded: 0.7-83.6 months (mean ± SD:25.1 ± 20.3).

Results: MATV-WB was an independent and statistically-significant predictor of overall survival (p < 0.001). The overall survival predictive ability of MATV-WB (C index: mean ± SD = 0.7071 ± 0.0009) was not worse than cTNM (C index: mean ± SD = 0.7031 ± 0.007) (Z = -0.143, p = 0.773). Estimated mean survival times of 56.3 ± 3.0 (95%CI:50.40-62.23) and 21.7 ± 2.2 months (95%CI:17.34-25.98) (Log-Rank = 77.48, p < 0.001), one-year survival rate of 86.8% and of 52.8%, and five-year survival rate of 53.6% and no survivors, were determined, respectively, for patients with MATV-WB < 49.5 and MATV-WB ≥ 49.5. Patients with MATV-WB ≥ 49.5 had a mortality risk 2.9-5.8 times higher than those with MATV-WB < 49.5 (HR = 4.12, p < 0.001). MATV-WB cutoff points were also determined for each cTNM stage: 23.7(I), 49.5(II), 52(III), 48.8(IV) (p = 0.029, p = 0.227, p = 0.025 and p = 0.001, respectively). At stages I, III and IV there was a statistically-significant difference in the estimated mean overall survival time between groups of patients defined by the cutoff points (p = 0.007, p = 0.004 and p < 0.001, respectively). At stage II (p = 0.365), there was a clinically-significant difference of about 12 months between the groups. In all cTNM stages, patients with MATV-WB ≥ cutoff points had lower survival rates. Combined clinical TNM-PET staging (cTNM-P) was then tested: Stage I < 23.7; Stage I ≥ 23.7; Stage II < 49.5; Stage II ≥ 49.5; Stage III < 52; Stage III ≥ 52; Stage IV < 48.8; Stage IV ≥ 48.8. cTNM-P staging presented a superior overall survival predictive ability (C index = 0.730) compared with conventional cTNM staging (C index = 0.699) (Z = -4.49, p < 0.001).

Conclusion: cTNM-P staging has superior prognostic value compared with conventional cTNM staging, and allows better stratification of NSCLC patients.